Structure-function coupling in the human brainstem

Abstract

The nuclei of the brainstem modulate neuronal activity throughout the central nervous system. Yet connectome reconstructions typically do not include the brainstem because it is notoriously difficult to image. As a result, the influence of the brainstem on structure-function coupling in the brain is unknown. Here we use high-resolution 7 Tesla magnetic resonance imaging (MRI) to reconstruct structural and functional brain connectomes encompassing cortex and 58 brainstem nuclei spanning the midbrain, pons, and medulla. We identify structural connectional profiles of individual brainstem nuclei to the cortex and find that they align with a spectrum of functions, spanning sensory and motor processing to higher-order cognition. Structural and functional connectivity in brainstem-augmented connectomes are positively correlated, and pairs of regions with direct anatomical projections display greater functional connectivity than pairs without. Structure-function coupling is heterogeneous across brainstem nuclei, with strong coupling in both modulatory and relay nuclei. Collectively, this work presents an initial step toward understanding how the brainstem shapes structure-function relationships in the brain.